| Objective: Leptin can regulate appetite and food intake,basal metabolism and insulin secretion and so on by binding and activating leptin receptor(LEPR).We aimed at exploring the association of polymorphisms in LEPR with type 2 diabetes mellitus(T2DM)and its related metabolic traits,discovering the relevant risk sites for T2 DM and providing reference for prevention and intervention of T2 DM.Methods: A 1:1 matched case-control study was conducted,with a total of 790 T2 DM patients as cases and 790 sex and age matched non-diabetic subjects as controls.All the subjects were selected from people who did routine examination in First Affiliated Hospital of Guangxi Medical University.MALDI-TOF-MS technique was used to genotype the two polymorphisms in LEPR(rs3806318,rs1327118).Plink and SPSS statistical software were used to analyze the association between the two polymorphisms and T2 DM as well as related metabolic traits,and odds ratio(OR)and 95% confidence interval(CI)were obtained.SHEsis online platform was used for linkage disequilibrium test and haplotype analysis.Multivariate dimensionality reduction(MDR)method was ultilized to analyze the interaction between gene and environment on T2 DM.Results:(1)The basic characteristics of the study subjects: Both of the average age of the cases and the controls were 63.82 ±9.49 years old.There were no significant statistical differences in sex,age,smoking,alcohol consumption,physical activity and low density lipoprotein(LDL)between cases and controls(P > 0.05).Body mass index(BMI),fasting blood glucose(FPG),2 hours postprandial blood glucose(2hPBG),glycosylated hemoglobin(HbA1c),total cholesterol(TC)and triglyceride(TG),systolic blood pressure(SBP)and diastolic blood pressure(DBP)of the case group were higher than that of the control group,while high density lipoprotein(HDL)was lower than the control group,the difference was statistically significant(P < 0.05).Logistic regression multivariate analysis showed that people with regular smoking(P = 0.033,OR = 1.586,95%CI = 1.038-2.425),24 ? BM I(27)28(P = 0.013,OR = 1.348,95%CI = 1.066-1.705),BMI ? 28(P < 0.001,OR = 2.379,95% CI = 1.038-2.425),hypertension(P = 0.035,OR = 1.273,95%CI = 1.038-2.425)and high triglyceride level(P < 0.001,OR = 2.100,95%CI = 1.653-2.668)had an increased risk of T2 DM,while those who had occasional drinking(P = 0.006,OR = 0.662,95%CI = 0.493-0.887),OR = 0.662,95%CI = 0.493-0.887)had a decreased risk of T2 DM.(2)Genotype and allele distributions: No statistical difference in allele and genotype distribution of rs3806318 and rs1327118 in LEPR were observed between cases and controls(P > 0.05).There was no association between polymorphisms of LEPR gene and T2 DM before and after adjusting BMI,smoking,drinking,TG and blood pressure(P > 0.05).Subgroup analysis showed that subjects with normal total cholesterol harboring the AG genotype of rs3806318 had a decreased risk of T2 DM compared with subjects with AA genotype(P = 0.033,OR = 0.664,95%CI = 0.455-0.968).For rs1327118,in population with normal blood pressure,normal LDL,no smoking and occasional drinking,the CG genotype was associated with a significant decreased risk of type 2 diabetes,with an OR of 0.678(P = 0.029,95%CI = 0.478-0.961),0.677(P = 0.024,95%CI = 0.481-0.951),0.736(P = 0.034,95%CI = 0.554-0.978)and 0.265(P < 0.001,95%CI = 0.128-0.548)when compared with CC genotype,respectively.(3)Haplotype analysis results showed that there was no significant difference in the distribution of the three haplotypes(AC,AG,GC)composed of rs3806318 and rs1327118 between cases and controls(P > 0.05).(4)MDR analysis results showed that the interaction between rs3806318 and rs1327118 and environmental factors in T2 DM susceptibility was not found in the analysis of the interaction between LEPR polymorphisms and environment.(5)Association between LEPR polymorphisms and metabolic traits: In cases,the subjects carrying the genotype CG+GG of rs1327118 had higher systolic blood pressure compared with those with CC genotype after adjustment for covariates(P = 0.003);However,there was no significant correlation between polymorphism of rs3806318 and metabolic traits(P > 0.05).In controls,the subjects carrying the genotype AG+GG of rs3806318 had a lower TG level compared with those with AA genotype after adjustment for covariates(P =0.026).However,there was no significant association between polymorphisms of rs1327118 and metabolic traits(P > 0.05).Conclusions:(1)Frequent smoking,overweight,fat,hypertension,and high triglyceride are risk factors for type 2 diabetes.Occasional drinking may have a protective effect on type 2 diabetes.(2)No significant association was observed between the two polymorphisms in LEPR gene and type 2 diabetes mellitus.There was no significant interaction between LEPR polymorphisms and environmental factors in T2 DM susceptibility.(3)Subjects with G allele of rs1327118 may be associated with increased SBP in T2 DM patients,and those carrying G allele of rs3806318 may be associated with decreased TC level in non-diabetic population. |
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